Parkinson's disease (PD) is a progressive, disabling neurodegenerative disorder with an annual national incidence of 70,000 and for which there is at present no diagnostic test. Radionuclide imaging of the dopamine transporter can measure neuronal loss noninvasively, as demonstrated by radiotracers labeled with the cyclotron-produced radionuclide iodine-123 under commercial development. Radiopharmaceuticals labeled with technetium-99m would be more practical for clinical application and commercial development, because of the lower cost and readier availability of technetium-99m. The goal of this project is to develop a 99mTC labeled probe of the dopamine transporter. We hypothesize that replacing the phenyl group of a phenyltropane with an isosteric aromatic metal complex will give a tracer with high affinity and low nonspecific binding. This application proposes to test proof of principle by synthesizing representative rhenium complexes and measuring in vitro binding and lipophilicity. Candidates with the highest affinity will be labeled with Tc-99m and the specific dopamine transporter binding of the radiolabeled complex will be measured. Phase II studies will follow up with in vivo binding by SPECT imaging of the Tc-99m complexes, developing labeling methods, for a "kit" product, and extending the structure-activity relationships. PROPOSED COMMERCIAL APPLICATION: The commercial availability of a Tc-99m SPECT agent for imaging of dopamine transporters will find wide application in Parkinson's disease to diagnose patients at risk, monitor progression of the disease, and to advance the development of effective preventive, palliative, and therapeutic treatments.